4006-776-356 出国就医服务电话

免费获得国外相关药品,最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Standard- Versus Reduced-dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Renal Transplantation

Standard- Versus Reduced-dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Renal Transplantation

Study Description
Brief Summary:
A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) versus standard-dose tacrolimus with reduced-dose MMF.

Condition or disease Intervention/treatment Phase
Disorder Related to Renal Transplantation Drug: Tacrolimus(reduced), Mycophenolate mofetil(standard) Drug: Tacrolimus(standard), Mycophenolate mofetil(reduced) Phase 4

Detailed Description:

A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group. For six months study period, graft function, the incidence of efficacy failure and adverse events were compared.

The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group: The study group (reduced-dose tacrolimus + standard-dose MMF) or the control group (standard-dose tacrolimus + reduced-dose MMF). Restricted block randomization was applied to this study and both the enrolled subjects and care providers were blinded until randomization was done. A difference in the mean estimated glomerular filtration rates (eGFR) of 16 mL/min/1.73m2 was considered a clinically meaningful margin of non-inferiority. A sample size of 108 for both groups was calculated for the primary endpoint by assuming a significance level of 0.025 with a power of at least 95% and adjusted for a potential dropout rate of 20%.

The primary efficacy endpoint was the renal graft function assessed with eGFR by MDRD formula at 6 months post-transplant. The secondary endpoints included (1) the incidence of treatment failure that included biopsy-confirmed acute rejection (BCAR), graft loss, death, or loss to follow-up until 6 months post-transplant; (2) recipients and grafts' survival rates; (3) 24-hour urine proteinuria and creatinine clearance at 6 months post-transplant. Recipients with clinical findings suggestive of acute rejection underwent biopsies before initiation or within 48 hours of anti-rejection therapy and biopsy specimens were graded according to Banff Classification criteria.

Safety endpoints included (1) all adverse event defined as any medical occurrence including worsening of a preexisting medical condition; (2) opportunistic infections; (3) malignancies; (4) abnormal laboratory findings; and (5) any abnormal physical findings or vital signs. Severe adverse events were defined as any adverse events with undesirable signs, symptoms, or medical conditions that met any one of the following criteria: 1) was fatal or life-threatening, 2) resulted in persistent or significant disability/incapacity, 3) required hospitalization or the prolongation of existing hospitalization, 4) was a congenital anomaly/birth defect, or 5) was an important medical event that might deteriorate the patient and require medical or surgical intervention to prevent one of the other outcomes listed above.18 All adverse events were coding using WHOART 2009 version.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparative Clinical Study of Reduced Dose of Tacrolimus and Standard Dose of Mycophenolate Mofetil vs. Conventional Dose of Tacrolimus and Reduced Dose of Mycophenolate Mofetil in De Novo Renal Transplant Recipients
Actual Study Start Date : July 29, 2014
Actual Primary Completion Date : November 11, 2016
Actual Study Completion Date : June 14, 2017
Arms and Interventions
Arm Intervention/treatment
Experimental: reduced-dose tacrolimus + standard-dose MMF
Tacrolimus dose was individually adjusted with a target trough blood level of between 3ng/mL and 8ng/mL throughout the study period (6 months after transplantation). MMF started within 72 hours after transplantation and the dose of MMF was 1.5~2.0g per day.
Drug: Tacrolimus(reduced), Mycophenolate mofetil(standard)
tacrolimus target trough blood level: 3~8ng/mL MMF dose: 1.5~2g/d
Other Name: TacroBell, MY-REPT

Active Comparator: standard-dose tacrolimus + reduced-dose MMF
Control group, target trough blood level was between 5ng/mL and 15ng/mL throughout the study period. MMF dose was 0.5~1g per day and MMF started within 72 hours after transplantation.
Drug: Tacrolimus(standard), Mycophenolate mofetil(reduced)
tacrolimus target trough blood level: 5~15ng/mL MMF dose: 0.5~1g/d
Other Name: TacroBell, MY-REPT

Outcome Measures
Primary Outcome Measures :
  1. renal graft function [ Time Frame: 6 months post-transplant ]
    assessed with eGFR by MDRD formula


Secondary Outcome Measures :
  1. incidence of treatment failure [ Time Frame: 6 months post-transplant ]
    biopsy-confirmed acute rejection (BCAR), graft loss, death, or loss

  2. recipients and grafts' survival rates [ Time Frame: 6 months post-transplant ]
    recipients and grafts' survival rates

  3. 24-hour urine proteinuria and creatinine clearance [ Time Frame: 6 months post-transplant ]
    24-hour urine proteinuria and creatinine clearance


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipients (aged 20-65) of a single (first or second) renal allograft from living or deceased donor.

Exclusion Criteria:

  • comprised of recipients with multiple organ transplants
  • double kidney transplant or organs donated after cardiac death
  • recipients previously organ transplanted except kidney
  • ABO-incompatible transplants
  • recipients with antibodies against the human leukocyte antigens of the donor organ
  • history of malignancy in the previous 5 years (except successfully treated localized non-melanoma skin cancer and thyroid cancer)
  • leukocyte counts of less than 2,500 per μL, or neutrophils less than 1,500 per μL, or platelets less than 50,000 per μL
  • evidence of active systemic infection requiring the use of antibiotics, human immunodeficiency virus infection, or chronic active hepatitis B or C
Contacts and Locations

Locations
Layout table for location information
Korea, Republic of
Chonbuk National University Hospital
Jeonju, Korea, Republic of
Gangnam Severance Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Ajou University Hospital
Suwon, Korea, Republic of
Sponsors and Collaborators
Ajou University School of Medicine
Investigators
Layout table for investigator information
Principal Investigator: Chang-Kwon Oh, M.D Department of surgery, Ajou University School of Medicine
Tracking Information
First Submitted Date  ICMJE May 28, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date May 30, 2019
Actual Study Start Date  ICMJE July 29, 2014
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
renal graft function [ Time Frame: 6 months post-transplant ]
assessed with eGFR by MDRD formula
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2019)
  • incidence of treatment failure [ Time Frame: 6 months post-transplant ]
    biopsy-confirmed acute rejection (BCAR), graft loss, death, or loss
  • recipients and grafts' survival rates [ Time Frame: 6 months post-transplant ]
    recipients and grafts' survival rates
  • 24-hour urine proteinuria and creatinine clearance [ Time Frame: 6 months post-transplant ]
    24-hour urine proteinuria and creatinine clearance
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Standard- Versus Reduced-dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Renal Transplantation
Official Title  ICMJE Comparative Clinical Study of Reduced Dose of Tacrolimus and Standard Dose of Mycophenolate Mofetil vs. Conventional Dose of Tacrolimus and Reduced Dose of Mycophenolate Mofetil in De Novo Renal Transplant Recipients
Brief Summary A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) versus standard-dose tacrolimus with reduced-dose MMF.
Detailed Description

A prospective, multicenter, open-label, randomized and parallel-group clinical trial was conducted at four transplant centers in Korea. The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group. For six months study period, graft function, the incidence of efficacy failure and adverse events were compared.

The total sample size was 108 and eligible patients were randomly assigned in a 1:1 ratio to either study or control group: The study group (reduced-dose tacrolimus + standard-dose MMF) or the control group (standard-dose tacrolimus + reduced-dose MMF). Restricted block randomization was applied to this study and both the enrolled subjects and care providers were blinded until randomization was done. A difference in the mean estimated glomerular filtration rates (eGFR) of 16 mL/min/1.73m2 was considered a clinically meaningful margin of non-inferiority. A sample size of 108 for both groups was calculated for the primary endpoint by assuming a significance level of 0.025 with a power of at least 95% and adjusted for a potential dropout rate of 20%.

The primary efficacy endpoint was the renal graft function assessed with eGFR by MDRD formula at 6 months post-transplant. The secondary endpoints included (1) the incidence of treatment failure that included biopsy-confirmed acute rejection (BCAR), graft loss, death, or loss to follow-up until 6 months post-transplant; (2) recipients and grafts' survival rates; (3) 24-hour urine proteinuria and creatinine clearance at 6 months post-transplant. Recipients with clinical findings suggestive of acute rejection underwent biopsies before initiation or within 48 hours of anti-rejection therapy and biopsy specimens were graded according to Banff Classification criteria.

Safety endpoints included (1) all adverse event defined as any medical occurrence including worsening of a preexisting medical condition; (2) opportunistic infections; (3) malignancies; (4) abnormal laboratory findings; and (5) any abnormal physical findings or vital signs. Severe adverse events were defined as any adverse events with undesirable signs, symptoms, or medical conditions that met any one of the following criteria: 1) was fatal or life-threatening, 2) resulted in persistent or significant disability/incapacity, 3) required hospitalization or the prolongation of existing hospitalization, 4) was a congenital anomaly/birth defect, or 5) was an important medical event that might deteriorate the patient and require medical or surgical intervention to prevent one of the other outcomes listed above.18 All adverse events were coding using WHOART 2009 version.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Disorder Related to Renal Transplantation
Intervention  ICMJE
  • Drug: Tacrolimus(reduced), Mycophenolate mofetil(standard)
    tacrolimus target trough blood level: 3~8ng/mL MMF dose: 1.5~2g/d
    Other Name: TacroBell, MY-REPT
  • Drug: Tacrolimus(standard), Mycophenolate mofetil(reduced)
    tacrolimus target trough blood level: 5~15ng/mL MMF dose: 0.5~1g/d
    Other Name: TacroBell, MY-REPT
Study Arms  ICMJE
  • Experimental: reduced-dose tacrolimus + standard-dose MMF
    Tacrolimus dose was individually adjusted with a target trough blood level of between 3ng/mL and 8ng/mL throughout the study period (6 months after transplantation). MMF started within 72 hours after transplantation and the dose of MMF was 1.5~2.0g per day.
    Intervention: Drug: Tacrolimus(reduced), Mycophenolate mofetil(standard)
  • Active Comparator: standard-dose tacrolimus + reduced-dose MMF
    Control group, target trough blood level was between 5ng/mL and 15ng/mL throughout the study period. MMF dose was 0.5~1g per day and MMF started within 72 hours after transplantation.
    Intervention: Drug: Tacrolimus(standard), Mycophenolate mofetil(reduced)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2019)
108
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 14, 2017
Actual Primary Completion Date November 11, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Recipients (aged 20-65) of a single (first or second) renal allograft from living or deceased donor.

Exclusion Criteria:

  • comprised of recipients with multiple organ transplants
  • double kidney transplant or organs donated after cardiac death
  • recipients previously organ transplanted except kidney
  • ABO-incompatible transplants
  • recipients with antibodies against the human leukocyte antigens of the donor organ
  • history of malignancy in the previous 5 years (except successfully treated localized non-melanoma skin cancer and thyroid cancer)
  • leukocyte counts of less than 2,500 per μL, or neutrophils less than 1,500 per μL, or platelets less than 50,000 per μL
  • evidence of active systemic infection requiring the use of antibiotics, human immunodeficiency virus infection, or chronic active hepatitis B or C
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03968588
Other Study ID Numbers  ICMJE 062KTP14-1C
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Chang kwon oh, Ajou University School of Medicine
Study Sponsor  ICMJE Ajou University School of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Chang-Kwon Oh, M.D Department of surgery, Ajou University School of Medicine
PRS Account Ajou University School of Medicine
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院